Vernolepin, a tricyclic elemanolide dilactone isolated from Vernonia hymenolepis A. Rich exhibits significant in vitro cytotoxicity and in vivo tumor inhibitory activity against Walker-256 rat carcinosarcoma. Although vernolepin is an exciting chemotherapeutic agent it is in short supply and a promising approach to obtain large quantities of the dilactone and derivatives of it appear to be by total synthesis. We herein propose a potentially practical synthesis of vernolepin starting from readily available materials. This synthesis utilizes several new synthetic procedures developed in our laboratories for the efficient elaboration of the salient structural features of vernolepin and related substances. The synthetic scheme is designed to allow a number of skeletal variations to be introduced into the basic vernolepin molecule. In addition, it permits isotopic labeling of vernolepin at a number of positions, an advantage which should be of value in biochemical studies. We have entered into a collaborative effort with the Department of Oncology at the University of Rochester to test synthetic vernolepin as well as intermediates leading to it. We also intend to submit the same compounds for testing to the Cancer Chemotherapy National Service Center.